Viruses Virus-like particles

The main objective of immunization against viruses is the prevention or modification of the disease. However, most of the existing classical vaccines are able to prevent the disease but are not so efficient in preventing infection (Sandhu, 1994 Ellis, 1999). The development of the recombinant DNA technology made possible the creation of vaccines that do not present the typical side effects of the vaccines of attenuated or inactivated viruses. Virus-like particles (VLPs) are one of the new vaccine strategies arising from recombinant DNA technology. 

Viruses Virus-like particles Self-assembled particles that are Drug or DNA FDA-approved Potential immunogenicity when... 

Bertolotti-Ciarlet, A., White, L. J., Chen, R., Prasad, B. V., and Estes, M. K. (2002). Structural requirements for the assembly of Norwalk virus-like particles. /. Virol. 76, 4044- 1055. 

Fig. 5.21 Cryoelectron micrograph of a single virus-like particle showing the well-defined protein coating of the 12 nm diameter Au nanoparticle (black disk). (Reprinted with permission from [98]. Copyright (2006) American Chemical Society).

Blessing, T., Remy, J.S., and Behr, J.P., Monomolecular collapse of plasmid DNA into stable virus-like particles, Proceedings of the National Academy of Sciences, United States of America, 1998, 95, 1427-1431. 

ErbacherP, Remy JS, Behr JP (1999) Gene transfer with synthetic virus-like particles via the integrin-mediated endocytosis pathway. Gene Ther 6 138-145... 

Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann ME. Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J Immunol 2004 172(3) 1777-1785. 

Molecular Recognition of Ligands by Native Viruses and Virus-Like Particles as Studied by NMR Experiments... 

Hewat, E. A., Booth, T. F. and Roy, R (1994). Structure of correctly self-assembled bluetongue virus-like particles. /. Struct. Biol. 112,183-191. 

Production of Core and Virus-Like Particles with Baculovirus Infected Insect Cells... 

In this paper the fundamental aspects of process development for the production of core and virus-like particles with baculovirus infected insect cells are reviewed. The issues addressed include particle formation and monomer composition, chemical and physical conditions for optimal cell growth, baculovirus replication and product expression, multiplicity of infection strategy, and scale-up of the process. Study of the differences in the metabolic requirements of infected and non-infected cells is necessary for high cell density processes. In the bioreactor, the specific oxygen uptake rate (OURsp) plays a central role in process scale-up, leading to the specification of the bioreactor operational parameters. Shear stress can also be an important variable for bioreactor operation due to its influence on cell growth and product expression. 

Keywords. Virus-like particles, Baculovirus, Insect cells. Process development. Mathematical models... 

Taking into account process integration, i.e. - cultivation and product purification, particle locaHsation is an important issue. Strategies to produce a secreted particle, either by manipulation of its composition or by co-expression of NS protein(s) will be also discussed, since this can lead to an easier purification process and to a decrease in product losses due to intracellular proteolysis. The production of Rotavirus-Hke particles and Bluetongue virus-like particles production will be used as examples to illustrate this point. 

The application of mathematical modelling to baculovirus infection and virus-like particle production was also successfully done to Parvovirus B19 viruslike particle production with two different baculovirus at low MOTs [18]. But in this model the same concepts proposed in the Licari and Bailey Model was applied, i. e. baculovirus infection follows Poisson distribution with mean and variance equal to a.MOI, but with co-infection with two single-vectors, each one encoding a specific viral protein. 

In addition to this, virus-like particles have been generated that contain a form of HBsAg that has been modified at the N-terminus so that it can be utilized to present T- and B-cell epitopes. The fact that the VLPs remained intact suggests that this alteration did not negatively affect the antigenic properties of the protein and that a multivalent response could be made possible. 

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